1. Field of the Invention
This invention relates to the use of certain naturally occurring alkyl or alkenyl phenols or their pharmaceutically acceptable base salts as antiobesity and fat-reducing agents. More particularly, it relates to a method of treating obesity in an animal, including human, by administering to the animal the foregoing alkyl or alkenyl phenols or their pharmaceutically acceptable base salts as well as to compositions containing the same which achieve the treatment of obesity.
Further, this invention relates to a method of reducing fat in an animal, including human, by administering to the animal the foregoing alkyl or alkenyl phenols or their pharmaceutically acceptable base salts as well as to compositions containing the same which achieve the reduction of fat.
2. Related Art
Obesity is the most prevalent, chronic, medical condition in our society and is directly or indirectly associated with a vast number of diseases including hypertension, diabetes, cardiovascular disease, gallstones, etc., as well as a diminished self-image with consequent psychological maladjustment in society. As such, obesity often leads to health hazards and shortened life expectancy.
The treatment of obesity remains an important and largely unachieved goal in medical science, and increased efforts to develop useful therapeutics are urgently needed The dilemma in the treatment of obesity is the pathological elevation of body weight which is mounted by the body's physiologic systems. When one system is perturbed, there is often a compensatory reaction which minimizes or negates the initial effect. Also, pharmacotherapy of obesity is at a very early stage compared with drug modalities available for treatment of other chronic diseases. Considerable progress, however, is being made in the quest of new therapeutics for the treatment of obesity which rely on one of the following pharmacologic approaches: (a) reduction of energy intake; (b) regulation of lipid and carbohydrate metabolism; and (c) enhancement of energy expenditure.
Compared with the (a) and (c) approaches, the (b) approach, which interferes with lipid or carbohydrate metabolism in the body, has not been fully exploited. One method to effectively modulate the lipid or carbohydrate metabolism is to suppress intestinal absorption of dietary lipids and/or carbohydrates. Inhibitors of intestinal lipases or glucosidases decrease the rate of the degradation of carbohydrates and triglycerides to absorbable monosaccharides and fatty acids, thereby normalizing body fat levels in obese animals.
Acarbose, is a pseudo-oligosaccharide of microbial origin and is known to competitively inhibit the action of several .alpha.-glucosidases within the gastrointestinal tract [W. Puls et al., Front. Horm. Res. 2, 235 (1980)]. Despite its potency in inhibition, symptoms of carbohydrate malabsorption and the resulting diarrhea have consistently been reported when acarbose is administered at high doses [R. Vargas et al., Clin. Pharmacol. Ther. 33, 216 (1983)]. Therefore, a search continues to find improved inhibitors of intestinal glucosidases and other carbohydrate digestive enzymes.
In veterinary areas, treatment of obese livestock or poultry has not traditionally been considered an important task compared with the treatment of obese humans. However, obesity in domestic pet animals arouses concern among pet owners who care for the animals' health and appearance. Furthermore, it has long been realized that reduction of fat content in broiler chickens, pigs and cattle is economically significant in view of increasing demand for lean meat.
Repartitioning agents such as cimaterol, ractopamine and porcine somatotropin are known to decrease fat deposition, increase lean tissue deposition, and improve efficiency of feed utilization. These agents are believed to alter the manner in which dietary energy intake is partitioned between lean and fat tissue in growing animals, thus favorably shifting the lean-fat ratio in poultry, cattle, sheep and swine. However, many of these agents are ineffective or cause adverse reactions, which limit their use. Where one of these agents may fail in an individual case, another may succeed. Thus, a continuing need for improved fat-reducing agents, which may be safe to animals and effective, is clearly evident.
Subsequent to this invention, there has been a report that a number of naturally occurring alkyl or alkenyl salicylic acids are thermogenic when tested in rat brown adipose tissue and may have a potential use as antiobesity agents (see Japan Kokai No. 2-104,530 to Okamoto et al., published April 17, 1990). However, there are no known reports concerning the inhibition of carbohydrate digestive enzymes such as intestinal .alpha.-glucosidase by the same salicyclic acids prior to the time of our invention. Nor are there any known reports concerning the use of those salicylic acids as a fat-reducing agent in human beings as well as in animals.